FDA Accepts NDA for Vismodegib

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Nov 9, 2011 - Genentech, a member of the Roche Group, today announced that the U.S. Food and Drug Administration (FDA) has accepted and filed the company's New Drug Application for vismodegib for the treatment of adults with advanced basal cell carcinoma (BCC) for whom surgery is considered inappropriate. The application has been granted Priority Review status and the FDA confirmed the action date is March 8, 2012.

Vismodegib is an investigational, oral, targeted medicine designed to selectively inhibit signaling in the Hedgehog pathway, which is implicated in more than 90 percent of BCC cases. BCC is the most common type of skin cancer, which is generally considered curable by surgery. However, when it advances, BCC can cause disfiguring and debilitating effects and in some patients can ultimately be life-threatening. Currently, there are no effective treatment options for advanced BCC.

“We are pleased the FDA has granted priority review for vismodegib and we look forward to working with the Agency on the review of the data,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “We hope to provide people with the first FDA-approved medicine for this potentially disfiguring, and in some cases fatal, disease as soon as possible.”

The vismodegib application is based on results from the pivotal ERIVANCE BCC study. The trial showed vismodegib substantially shrank tumors or healed visible lesions (objective response rate, or ORR) in 43 percent of patients with locally advanced BCC (laBCC) and 30 percent of patients with metastatic BCC (mBCC), as assessed by independent review, the primary endpoint of the study.

The ORR as assessed by study investigators, a secondary endpoint, was 60 percent for laBCC and 46 percent for mBCC. The median progression-free survival (PFS) by independent review for both metastatic and locally advanced BCC patients was 9.5 months.

The most common drug-related adverse events were muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhea. Serious adverse events (SAEs) were observed in 26 patients (25 percent). Four patients (4 percent) had SAEs that were considered to be related to vismodegib, including one case each of: blocked bile flow from the liver (cholestasis), dehydration with loss of consciousness (syncope), pneumonia accompanied by an inability of the heart to pump enough blood (cardiac failure) and a sudden arterial blockage in the lung (pulmonary embolism). Fatal events were reported in seven patients (7 percent); none were considered by investigators to be related to vismodegib. In all cases, patients had other pre-existing diseases or symptoms that were related to their presumed cause of death.

In order to provide people with advanced BCC who are appropriate candidates access to vismodegib while the application is reviewed by the FDA, the company is conducting an expanded patient access study in the United States. For more information, patients and doctors can contact the Genentech clinical trial call center at 888-662-6728 or visit http://www.clinicaltrials.gov.

About Basal Cell Carcinoma and the Hedgehog Pathway

According to the American Cancer Society, BCC accounts for approximately 80 percent of all diagnosed skin cancers. The disease is generally considered curable if the cancer is restricted to a small area of the skin. However, in a very small group of people, if the disease is left untreated or recurs after surgery, it becomes locally advanced, and the cancer may invade further into surrounding tissues such as sensory organs (ears, nose and eyes), bones or other tissues. In a small proportion of patients (estimated at less than one percent of those affected), BCC can metastasize, spreading to other parts of the body.

The Hedgehog signaling pathway plays an important role in regulating proper growth and development in the early stages of life and becomes less active in adults. In addition to BCC, mutations in the pathway that reactivate Hedgehog signaling are seen in several types of cancer.

About the ERIVANCE BCC/SHH4476g Study

ERIVANCE BCC is an international, single-arm, multicenter, two-cohort, open-label Phase II study that enrolled 104 patients with advanced BCC, including laBCC (71) and mBCC (33). laBCC patients had lesions that were inappropriate for surgery (inoperable, or for whom surgery would result in substantial deformity) and for which radiotherapy was unsuccessful or contraindicated. mBCC was defined as BCC that had spread to other parts of the body, including the lymph nodes, lungs, bones and/or internal organs. Study participants received 150mg vismodegib orally, once daily until disease progression or intolerable toxicity.

About Vismodegib (RG3616/GDC-0449)

Vismodegib is an investigational medicine designed to selectively inhibit abnormal signaling in the Hedgehog pathway, which is an underlying molecular driver of BCC. Roche and Genentech are also evaluating vismodegib in a Phase II trial in people with operable forms of BCC.

Roche is developing vismodegib under a collaboration agreement with Curis, Inc. Vismodegib was discovered by Genentech and jointly validated by Genentech and Curis through a series of preclinical studies. Through this collaboration, Genentech (United States), Roche (ex-United States excluding Japan) and Chugai Pharmaceuticals (Japan) are responsible for the clinical development and commercialization of vismodegib. Curis is eligible to receive cash payments upon the successful achievement of specified clinical development and regulatory approval milestones, as well as royalties upon commercialization of vismodegib.

About Genentech

Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.